Stimulation of tumour angiogenesis by proximal wounds: spatial and temporal analysis by MRI.
We show here, using high-resolution magnetic resonance imaging, that injured tissue provides a favourable milieu for the neovascularization and growth of C6 glioma spheroids, implanted subcutaneously in nude mice. Moreover, the presence of micro-tumours in an injured tissue inhibited the healing process, leaving an open persistent wound. In correlation with the induced angiogenesis of implanted spheroids in the presence of proximal wounds, a shorter lag period was observed for initiation of tumour growth. This effect was restricted spatially and was observed only for wounds within 5 mm from the tumour. In such proximal wounds, angiogenesis was enhanced in the first days after injury, and vessel regression, which normally starts 4 days after injury, did not occur. Injury causing interference to tumour perfusion promoted tumour vascularization and growth even for more remote incisions, possibly by activating stress-induced angiogenesis. The kinetics of vascularization and growth of these wound-tumour systems sheds light on the clinical observations of increased probability of metastatic recurrence and stimulated regrowth of residual tumour in the site of surgical intervention. High-resolution magnetic resonance imaging could detect the aberrant angiogenic activity of these tumour-wound systems as early as 1 week after injury.
Abramovitch
R
R
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
Marikovsky
M
M
Meir
G
G
Neeman
M
M
D000818:Animals; D005910:Glioma / Q000098:blood supply*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000209:etiology*; D051381:Rats; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D014947:Wounds and Injuries / Q000503:physiopathology*